Results

Viral load analysis: Lower limit of detection = 500 copies/ml

Results (Contd.)

• 72% (21/29) of patients with baseline viral loads < 80,000 copies/ml and 80% (20/25) of patients with baseline viral loads > 80,000 copies/ml were below the limit of detection after 12 months
  
  
• Median rises in CD4+ cell count of 195 cells/mm3 and 230 cells/mm3 were observed in the low and high viral load groups, respectively.

Conclusion: This 1 year study showed that the combination of stavudine + lamivudine + nevirapine is effective and safe for patients with low as well as high viral loads.

Ref: 7th European Conference on Clinical Aspects and Treatment of HIV infection; Lisbon 1999. Abstract 518

Study 2

Study design: Open-label, prospective trial

Regimen: Nevirapine + stavudine + lamivudine

Population: 25 antiretroviral-naïve patients

Mean baseline viral load: 160, 000 copies/ml

Mean baseline CD4 count: 259 cells/mm3

Results: 87% of patients had undetectable viral loads at 33-44 weeks.

Conclusion: "If combinations such as this prove to have sufficient long-term effectiveness, they should provide a useful alternative to protease inhibitor containing regimens in selected patients."

Ref: 5th Conference on Retroviruses and Opportunistic Infections, Chicago 1998. Abstract 696.

Study 3
Background: The male genital tract represents a distinct "compartment" in which viral replication and evolution differ from those in blood. One determinant of viral evolution may be the concentration of antiviral drugs achieved in this compartment. Poor drug penetration may lead to sub-optimal viral suppression and predispose to the more rapid emergence of drug-resistant variants within the genital tract. Further, the seminal viral load also influences the probability of sexual transmission of HIV.

Objective: The objective of this study was to determine the concentrations of nevirapine, lamivudine and stavudine in seminal and blood plasma in HIV-1-infected men.

Methods: 12 HIV-1 infected men on nevirapine-containing regimens including lamivudine (n=8) or stavudine (n=11) provided 23 blood plasma and 22 seminal plasma samples for drug concentration and determination of viral load.

Results: The concentrations of nevirapine attained in the semen are approximately 60% of those in the blood plasma throughout the 12 hour dosing period. Absolute seminal plasma nevirapine concentrations were approximately 100-fold greater than the nevirapine IC90 for wild-type virus (0.016 mg/ml). The concentrations of lamivudine and stavudine in seminal plasma were similar to or higher than concentrations in blood plasma.

The median seminal plasma viral load for all patients was less than 800 copies/ml. The median blood plasma viral load was less than 400 copies/ml.

Conclusion: Thus, nevirapine, stavudine and lamivudine are able to achieve good concentrations within the genital tract, and have the potential to inhibit viral replication in this important body compartment. This data may well have implications for the evolution of drug-resistant virus within the genital tract.

Ref: AIDS 2000; 14: 1979-84

INDICATIONS
Triomune is indicated for the treatment of HIV infection, once patients have been stabilized on the maintenance regimen of nevirapine 200 mg bd, and have demonstrated adequate tolerability to nevirapine.


DOSAGE AND ADMINISTRATION

Adults
Triomune - 30
1 tablet twice daily for patients weighing < 60 kg

Triomune - 40
1 tablet twice daily for patients weighing > 60 kg

Triomune should not be administered to patients who have just initiated therapy with nevirapine. This is because an initial lead-in dosing of 200 mg nevirapine once daily for 2 weeks is recommended. Following this lead-in dose, a dose escalation (maintenance dose) to 200 mg nevirapine bd may be carried out in the absence of any hypersensitivity reactions (e.g. rash, liver function test abnormalities; see Warnings and Precautions).

Monitoring of patients
Clinical chemistry tests, which include liver function tests, should be performed prior to initiating lead-in nevirapine therapy and at appropriate intervals during therapy (see Warnings and Precautions).

Dosage Adjustment
Lamivudine
Because it is a fixed-dose combination, Triomune should not be prescribed for patients requiring dosage adjustment, such as those with low body weight
(<50 kg).

Nevirapine
Triomune should be discontinued if patients experience severe rash or a rash accompanied by constitutional findings (See Warnings and Precautions). Patients experiencing mild to moderate rash during the 14-day lead-in period of 200 mg/day should not have their nevirapine dose increased or start therapy with Triomune until the rash has resolved (see Warnings and Precautions).

Triomune administration should be interrupted in patients experiencing moderate or severe liver function tests abnormalities (excluding GGT), until the liver function test elevations have returned to baseline. Nevirapine (using Nevimune Tablets) may then be restarted at 200 mg per day. Increasing the daily dose to 200 mg twice daily (using Triomune) should be done with caution, after extended observation. Nevirapine should be permanently discontinued if moderate or severe liver function test abnormalities recur (see Warnings and Precautions).

Patients who interrupt nevirapine dosing for more than 7 days should restart the recommended dosing, using one 200 mg Nevimune tablet daily for the first 14 days (lead-in) in combination with the other antiretrovirals, followed by 200 mg twice daily using Triomune in the absence of any signs of hypersensitivity.

No data are available to recommend a dosage of nevirapine in patients with hepatic dysfunction, renal insufficiency or undergoing dialysis.